Shu-ichi Okamoto1, Stuart A Lipton2. 1. Neuroscience and Aging Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Neurosciences, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA, USA. Electronic address: sokamoto@sbmri.org. 2. Neuroscience and Aging Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Neurosciences, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA, USA. Electronic address: slipton@ucsd.edu.
Abstract
BACKGROUND: Nitric oxide (NO) is a pleiotropic messenger molecule. The multidimensional actions of NO species are, in part, mediated by their redox nature. Oxidative posttranslational modification of cysteine residues to regulate protein function, termed S-nitrosylation, constitutes a major form of redox-based signaling by NO. SCOPE OF REVIEW: S-Nitrosylation directly modifies a number of cytoplasmic and nuclear proteins in neurons. S-Nitrosylation modulates neuronal development by reaction with specific proteins, including the transcription factor MEF2. This review focuses on the impact of S-nitrosylation on neurogenesis and neuronal development. MAJOR CONCLUSIONS: Functional characterization of S-nitrosylated proteins that regulate neuronal development represents a rapidly emerging field. Recent studies reveal that S-nitrosylation-mediated redox signaling plays an important role in several biological processes essential for neuronal differentiation and maturation. GENERAL SIGNIFICANCE: Investigation of S-nitrosylation in the nervous system has elucidated new molecular and cellular mechanisms for neuronal development. S-Nitrosylated proteins in signaling networks modulate key events in brain development. Dysregulation of this redox-signaling pathway may contribute to neurodevelopmental disabilities such as autism spectrum disorder (ASD). Thus, further elucidation of the involvement of S-nitrosylation in brain development may offer potential therapeutic avenues for neurodevelopmental disorders. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
BACKGROUND:Nitric oxide (NO) is a pleiotropic messenger molecule. The multidimensional actions of NO species are, in part, mediated by their redox nature. Oxidative posttranslational modification of cysteine residues to regulate protein function, termed S-nitrosylation, constitutes a major form of redox-based signaling by NO. SCOPE OF REVIEW: S-Nitrosylation directly modifies a number of cytoplasmic and nuclear proteins in neurons. S-Nitrosylation modulates neuronal development by reaction with specific proteins, including the transcription factor MEF2. This review focuses on the impact of S-nitrosylation on neurogenesis and neuronal development. MAJOR CONCLUSIONS: Functional characterization of S-nitrosylated proteins that regulate neuronal development represents a rapidly emerging field. Recent studies reveal that S-nitrosylation-mediated redox signaling plays an important role in several biological processes essential for neuronal differentiation and maturation. GENERAL SIGNIFICANCE: Investigation of S-nitrosylation in the nervous system has elucidated new molecular and cellular mechanisms for neuronal development. S-Nitrosylated proteins in signaling networks modulate key events in brain development. Dysregulation of this redox-signaling pathway may contribute to neurodevelopmental disabilities such as autism spectrum disorder (ASD). Thus, further elucidation of the involvement of S-nitrosylation in brain development may offer potential therapeutic avenues for neurodevelopmental disorders. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
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